A Realistic Computer-Simulated Brain Phantom for Evaluation of PET Charactenstics

To evaluate accurately the imaging characteristics of positron emission tomography (PET), a realistic computer-simulated brain phantom was developed. A cross-sectional slice from a human cadaver brain was chosen for its combination of gray matter, white matter, and cerebrospinal fluid (CSF) regions. The slice was photographed and digitized into a gray-level image with a video digitizer, boundary edges were located around cerebral structures in the digitized image, and each structural region was assigned a uniform pixel value dependent on both the cerebral parameter (e.g., blood flow, oxygen uptake, metabolic rate) under investigation and the type of structure (gray matter, white matter, CSF). Line integrals through the regions were generated at various angular and transverse positions according to specific physical characteristics (such as detector line-spread function) of a tomographic scanner configuration to create a set of simulated but realistic projection measurements. The set of projection measurements can be processed with any standard reconstruction program to create a tomographic image to reveal the effects of various PET characteristics. Investigations with this computer-simulated brain phantom have demonstrated its usefulness for examining the interrelations among neuroanatomical structure volume, tomographic spatial resolution, partial volume effect, and nonlinear parameter estimation. Transportability of the simulated phantom and the procedure to other medical imaging environments is described, and limitations of this simulation procedure are discussed.     

Are quantum dots ready for in vivo imaging in human subjects?

Nanotechnology has the potential to profoundly transform the nature of cancer diagnosis and cancer patient management in the future. Over the past decade, quantum dots (QDs) have become one of the fastest growing areas of research in nanotechnology. QDs are fluorescent semiconductor nanoparticles suitable for multiplexed in vitro and in vivo imaging. Numerous studies on QDs have resulted in major advancements in QD surface modification, coating, biocompatibility, sensitivity, multiplexing, targeting specificity, as well as important findings regarding toxicity and applicability. For in vitro applications, QDs can be used in place of traditional organic fluorescent dyes in virtually any system, outperforming organic dyes in the majority of cases. In vivo targeted tumor imaging with biocompatible QDs has recently become possible in mouse models. With new advances in QD technology such as bioluminescence resonance energy transfer, synthesis of smaller size non-Cd based QDs, improved surface coating and conjugation, and multifunctional probes for multimodality imaging, it is likely that human applications of QDs will soon be possible in a clinical setting.     

Protein folding transition states: elicitation of Hammond effects by 2,2,2-trifluoroethanol

Adaptation of the techniques of classical physical-organic chemistry to the study of protein folding has led to our current detailed understanding of the transition states. Here, we have applied a series of structure--activity relationships to analyse the effects on protein folding transition states of 2,2,2-trifluoroethanol (TFE), a reagent that is usually assumed to act by stabilising secondary structure. The folding and unfolding of the highly alpha-helical tetramerisation domain of p53 provides a useful paradigm for analysing its effects on kinetics: The first step of its folding consists of an association reaction with little, if any, formation of secondary structure in the transition state; and the final step of the folding reaction involves just the formation of bonds at subunit interfaces, with the alpha-helical structure being completely formed. We have systematically measured the effects of TFE on two sets of structure--activity relationships. The first is for Phi values, which measure the degree of non-covalent bond formation at nearly every position in the transition state. The second is for relative effects of the denaturant, guanidinium chloride, on kinetics and equilibria, which measure the gross position of the transition state on the reaction co-ordinate. We find that TFE modulated the kinetics by a variety of effects other than that on secondary structure. In particular, there were Hammond effects, movement of the position of the transition state along the reaction co-ordinate, which either significantly speeded up or slowed down protein unfolding, depending on the particular mutant examined. The gross effects of TFE on protein folding kinetics are thus not a reliable guide to the structures of transition states.     

Avoidance response of juvenile Pacific treefrogs to chemical cues of introduced predatory bullfrogs

Bullfrogs (Rana catesbeiana), native to eastern North America, were introduced into Oregon in the 1930's. Bullfrogs are highly efficient predators that are known to eat a variety of prey including other amphibians. In laboratory experiments, we investigated whether juvenile Pacific treefrogs (Hyla regilla) recognize adult bullfrogs as a predatory threat. The ability of prey animals to acquire recognition of an introduced predator has important implications for survival of the prey. We found that treefrogs from a population that co-occurred with bullfrogs showed a strong avoidance of chemical cues of bullfrogs. In contrast, treefrogs from a population that did not co-occur with bullfrogs, did not respond to the bullfrog cues. Additional experiments showed that both populations of treefrogs use chemical cues to mediate predation risk. Treefrogs from both populations avoided chemical alarm cues from injured conspecifics.